Do you want to live a longer life in good health? Simple practices can make some difference, such
as exercise or calorie restriction. But over the long haul all that really matters is medical biotechnology:
progress towards repair and reversal of the known root causes of aging. The sooner these
treatments arrive, the more lives will be saved. Find out how to help »

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

______________________________

CONTENT

- Enthusiasm for the Slow Road
- The Oblivious Public
- More on the Russia 2045 Initiative
- Discussion
- Latest Headlines from Fight Aging!

ENTHUSIASM FOR THE SLOW ROAD

Despite tremendous progress in public attitudes towards longevity science in the research and funding community over the past decade, it is still the case that the vast majority of funds and interest goes towards strategies that won't achieve much of anything for those of us in middle age today. This must change:

"Where there is enthusiasm for addressing the process of aging in the life science research and funding communities, that enthusiasm is still overwhelmingly directed towards the slow, incremental road. Which is to say, plans such as: (a) Modestly slow aging by reverse engineering calorie restriction to build a medication that captures some of its effects. (b) Modestly slow aging by reverse engineering the difference between long-lived and short-lived people and build a medication that captures some of these effects. (c) Modestly slow aging by reverse engineering the differences between long-lived and short-lived mammalian species and build a medication that captures some of these effects.

"These are all enormous projects of great complexity, stretching the bounds of the research community, that will likely take two or more decades to come to fruition (see how long the investigation of sirtuins has lasted to date, with no payoff in sight...) and yet even if they exceed their goals they will produce only a marginal benefit at the end of it. Likely no benefit at all for people who have grown old waiting - slowing aging does little for a person who is already mostly aged to death.

"As regular readers know, there is another path forward - the SENS vision of biotechnologies based on repair of damage rather than slowing down the rate of damage. This is likely to be no more costly than the research plans outlined above, and yet will produce at the end of the day a true cure for aging, not just a marginal benefit and a couple of extra years of life. This is the case because the plans above require understanding and safely producing new long-term working states in human metabolism - an undertaking of massive proportions. The SENS approach in contrast requires that researchers revert the short list of known age-related changes in human metabolism to restore it to the state it held when young; no new working state, just keep the metabolism that already works and repair it every so often.

"One prominent insanity amongst the many in this madhouse world we live in is that it has required a major and ongoing campaign of hard work and persuasion to convince even a tiny minority of researchers and funding sources to work on the obviously better plan (SENS) rather than the obviously worse plan (slowing aging a little bit). This is the most important strategic debate in medicine and biotechnology today, and for the foreseeable future, as the outcome will determine how long we all live."

THE OBLIVIOUS PUBLIC

Outside the scientific community, and again despite tremendous progress in advocacy over the past decade, there remains a great deal of work to do as well:

"At the end of a post on the science of aging, filmmaker Robert Kane Pappas says the following on the goal of greatly extending human life: 'Actual age reversal was something - that, when I first heard of it 5 years ago - I put in the category of time travel and ghosts. [But] after 5 years of interviewing the researchers and poking around labs with my camera, it is not a question of if but when. The general population has little idea of what is about to befall them.'

"Which is both true and a problem. From an advocate's point of view, I'd say that unless a much larger portion of the public gains an understanding of longevity, the level of support will not rise far enough to generate the large sums of money needed for meaningful progress within the next 20 to 30 years. Outside of stem cell medicine and cancer research, the necessary research programs to build rejuvenation biotechnology are somewhere between fringe, anemic, and non-existent, relatively speaking - and it's only the dedicated efforts of groups like the Methuselah Foundation and SENS Foundation that have boosted these research projects to be more than non-existent. The present few million dollars a year is a lot in one sense, but a drop in the bucket in comparison to the the hundred of millions that are necessary for real progress.

"Given that, I feel I can say that if the first fruits of longevity science come as a surprise to the world at large, to the average fellow in the street, then those advances will likely be faltering and far less imposing than might have been possible. On the large scale progress in science and medical technology is a numbers game: the more public support there is, the easier it becomes to raise funding, the more researchers become interested in working in the field, and the more entrepreneurs step forward ... and the wheel turns faster as a result. To gain that greater public support requires persuasion, communication, and education - informal and otherwise - are thus it is these line items that are the roots of progress when looking at breadth of society and a length of decades."

"To my eyes, the most interesting aspect of this Russia 2045 initiative is that, unlike any other serious proposal I'm aware of, their focus is on getting out of biology and into machine bodies as rapidly as possible. ... In essence, this is a course to throw away as much of the body as possible as soon as possible - a path based on a different set of preconceptions about difficulty and efficiency on the road leading to an artificial brain hosting a once-biological human mind. If aiming for life spans of thousands of years, this is the exactly same place we'll get to in the end even if we start out by maintaining our biological bodies and brains for as long as possible through rejuvenation biotechnologies. ... In essence the Russia 2045 strategy swaps most of the challenges and research goals of rejuvenation biotechnology for a different set of challenges and research goals regarding brain-machine interfaces, supporting the brain outside the body, and maintaining the brain against aging while doing it. Whether this makes for an easier problem space is very open to debate.

"But on with the more recent news: there was a Global Future 2045 conference last month, organized by the same group: 'Global Future 2045' is a nonprofit organization with the goal of creating a network community with the world's leading scientists in the field of life extension and to support them as an investment hub, contributing to various projects. ... You should peruse the presentation videos, as they give a fair idea as to the focus: to transcend biology as rapidly as possible, and outline the details of that path in much the same spirit as the SENS platform discusses how to retain one's biology in good working condition for as long as desired.

"A Wired article provides a little more background on this organization and its backer: Dmitry Itskov, a 31-year-old Russian media mogul, [has] a massive, sci-fi-esque venture of his own ... Itskov's plan: Construct robots that'll (within 10 years, he hopes) actually store a human's mind and keep that consciousness working. Forever. 'This project is leading down the road to immortality,' Itskov, who founded New Media Stars, a Russian company that runs several online news outlets, tells Danger Room. 'A person with a perfect Avatar will be able to remain part of society. People don't want to die.' ... Until now, most of the work on Itskov's Avatar has taken place in Russia, where he claims to have hired 30 researchers - all of them paid out of his own deep pockets. Now, Itskov plans to take the mission global. 'I want to collaborate with scientists from around the world,' he says. 'This is a new strategy for the future; for humanity.'"

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

______________________________

LATEST HEADLINES FROM FIGHT AGING!

MORE SUPPORT FOR THE MEMBRANE PACEMAKER HYPOTHESIS OF AGING
Friday, March 2, 2012https://www.fightaging.org/archives/2012/03/more-support-for-the-membrane-pacemaker-hypothesis-of-aging.php
The membrane pacemaker hypothesis suggests that longevity differences between species are largely determined by the resistance to oxidative damage exhibited by important cell membranes - such as those in mitochondria. Here is some evidence to suggest that this holds up within a species too: "Membrane unsaturation plays an important role in the aging process and the determination of inter-species animal longevity. Furthermore, the accumulation of oxidation-derived molecular damage to cellular components particularly in the nervous and immune systems over time leads to homeostasis loss, which highly influences age-related morbidity and mortality. In this context, it is of great interest to know and discern the degree of membrane unsaturation and the steady-state levels of oxidative damage in both physiological systems from long-lived subjects. In the present work, adult (28 ± 4 weeks), old (76 ± 4 weeks) and exceptionally old (128 ± 4 weeks) BALB/c female mice were used. Brain and spleen were analysed for membrane fatty acid composition and specific markers of protein oxidation, glycoxidation and lipoxidation damage ... The results showed significantly [higher membrane resistance to lipid peroxidation and lower lipoxidation-derived molecular damage brain and spleen in] exceptionally old animals when compared to old specimens ... In addition, the higher levels of the glycoxidation-derived marker observed in exceptionally old animals, as well as in adult mice, could be considered as a good indicator of a better bioenergetic state of these animals when compared to the old group. In conclusion, low lipid oxidation susceptibility and maintenance of adult-like protein lipoxidative damage could be key mechanisms for longevity achievement."

ON MITOCHONDRIAL DYSFUNCTION AND SKIN AGING
Friday, March 2, 2012https://www.fightaging.org/archives/2012/03/on-mitochondrial-dysfunction-and-skin-aging.php
An open access commentary at Impact Aging: "There is a lively discussion going on as to whether oxidative stress is or is not a cause of (accelerated) aging, fuelled to a significant extent by the finding from Arlan Richardson's group that mice heterozygous for the mitochondrial superoxide dismutase SOD2 showed increased oxidative stress, increased cancer incidence but not accelerated ageing. A new twist to this story was introduced recently when it was shown that connective tissue-specific SOD2 knockouts developed multiple signs of progeria including short lifespan, associated with up-regulation of the cell senescence marker p16INK4A. Mitochondrially generated oxidative stress is both an established cause and a relevant consequence of cell senescence, frequencies of senescent cells in connective tissue increase during mice aging, and destruction of senescent cells can 'cure' some age-related tissue dysfunction. A paper by Judith Campisi's and Simon Melov's groups recently published in Aging now further explores the connection between oxidative stress, cell senescence and aging. The authors demonstrate that mitochondrial dysfunction occurs in the epidermis of old (2 years) mice ... These data enforce two central hypotheses in the field, namely that of mitochondrial dysfunction as a cause of cell senescence, and of cell senescence as a relevant contributor to mammalian aging ... However, a fascinating question remains: Is it really Reactive Oxygen Species (ROS) arising from mitochondria that promote cellular senescence in this model?"

THE PAST IS NOT A GOOD PREDICTOR OF THE FUTURE
Thursday, March 1, 2012https://www.fightaging.org/archives/2012/03/the-past-is-not-a-good-predictor-of-the-future.php
We are far from the first generation to have looked at the state of science and postulated that we can significantly extend human life span through some specific means - but we are the first generation to have possession of the necessary scientific knowledge to be correct in our evaluation. That we have this knowledge is why you can't just look at the long history of predictions of longevity and say "we're just another generation that will be disappointed - it's all more of the same." The past is a great place to look if you want to predict the future of politics, but a terrible resource for predicting the future of technology. There is an enormous difference between the state of life science of today and the nascent biotechnology of the 1970s and advocates like Timothy Leary - and not to mention the science of the early 20th century as is referenced in this article: "It might seem as if a magic [longevity-enhancing] pill isn't so far off. But before we get too cheery about the prospects for these discoveries, it's useful to be reminded of the many longevity 'breakthroughs' that have come and gone in the past. One such potential advance was hailed in the November 1929 issue of Technology Review, in an essay called 'Forestalling Death: The Cow's Contribution to Human Longevity' ... In the previous 125 years, Tobey observed, average life span had risen from the low 30s to the upper 50s. This was primarily due to reductions in infectious disease and in the infant death rate ... It wasn't enough to simply reduce a threat such as infectious disease - it was imperative that we find something we could add to our lives, or maybe simply increase our intake of something we were already consuming. He felt recent research might have uncovered just such a substance. ... He pointed to recent experiments at Columbia University, wherein one set of rats had been given an 'adequate diet' of one-sixth dried whole milk and five-sixths whole wheat. An 'optimal diet' group, meanwhile, received double the milk and less wheat. The average duration of life was almost exactly ten percent greater in those subjects receiving the optimal diet ... Is it possible that we have had the fountain of youth within our grasp throughout the ages that man has been seeking this liquid phantasm? Milk has always been recognized as the one most nearly perfect food ... but apparently it possesses hitherto undreamed of virtues." And so on: the end result is more of the oral fixation that seems to so dominate our culture - in the popular imagination everything of significance must be something that we put in our mouths and consume. Most important medicine, of course, is nothing of the sort.

REDUCING MUSCLE LOSS WITH AGING IN MICE
Thursday, March 1, 2012https://www.fightaging.org/archives/2012/03/reducing-muscle-loss-with-aging-in-mice.php
Another potential method to treat or minimize the progession of sarcopenia: researchers "report that a family of protein transcription factors, called 'Forkhead (Fox0)' plays a significant role in the regulation of skeletal muscle mass. Specifically, they found that interfering with the activity of these transcription factors prevents muscle wasting associated with cancer and sepsis, and even promotes muscle growth. This discovery is likely to be relevant to any disease, condition or lifestyle that leads to muscle wasting, including voluntary inactivity. [Researchers] genetically inhibited the activity of 'Forkhead boxO' proteins, or 'FoxO,' in the skeletal muscle of healthy control mice, septic mice, and mice with cancer. The loss of muscle mass in those with cancer and sepsis was significantly decreased by inhibition of FoxO activity. In healthy control animals inhibiting FoxO activity caused an increase in muscle cell size which occurred as a result of protein synthesis. ... FoxO proteins may provide a target for therapies aimed at reducing muscle wasting and thus improving the quality of life and survival rates for patients with many different diseases."

ANOTHER LONGEVITY GENE IN NEMATODES
Wednesday, February 29, 2012https://www.fightaging.org/archives/2012/02/another-longevity-gene-in-nematodes.php
A mere 40% extension of life span in nematode worms via a novel method is a part of the general background noise of aging research nowadays: "The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to [longevity-enhancing genes]. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor."

AUBREY DE GREY ON THE ENGINEERING PHILOSOPHY OF SENS
Wednesday, February 29, 2012https://www.fightaging.org/archives/2012/02/aubrey-de-grey-on-the-engineering-philosophy-of-sens.php
The core point of SENS, the Strategies for Engineered Negligible Senescence, is explained in this short interview: "Could you elaborate on the idea mentioned on SENS: that it isn't necessary to know, from an 'engineering' perspective, everything about the degenerative processes that occur at the cellular level in order to treat aging in the way you envision? ... The basic point we're making there is to contrast the regenerative approach with the more traditional idea of trying to make metabolism create molecular and cellular damage more slowly. In order to do the latter, we would need to understand our biology massively better than we do at present, so as to avoid creating unforeseen side-effects. By contrast, with the regenerative approach we don't need to know much about how damage comes about: it's enough just to characterize the damage itself, so as to figure out ways to repair it. We're effectively sidestepping our ignorance of metabolism. ... Rejuvenation biotechnologies are simply regenerative therapies that pre-empt the diseases and disabilities of old age. They consist of molecular, cellular or whole-organ interventions that restore the structure of the target to something like how it was in early adulthood. This includes a variety of stem cell therapies, and also tissue engineering to create artificial organs. At SENS Foundation we don't work much on those types of therapy, because they're being very capably pursued elsewhere; rather, we focus on the more neglected but equally vital components of this 'divide-and-conquer' approach to combating aging. For example, we have a large project aimed at eliminating 'molecular garbage' from cells - indigestible material whose accumulation leads to diseases like atherosclerosis and macular degeneration - by introducing non-human enzymes to augment the body's natural ability to break down unwanted by-products of metabolism."

RAPAMYCIN SLOWS AGING IN MICE (PDF)
Tuesday, February 28, 2012https://www.fightaging.org/archives/2012/02/rapamycin-slows-aging-in-mice-pdf.php
Here is a commentary on rapamycin research results (only available in PDF format, I'm afraid to say), which you might compare with an earlier commentary on the same work: "Anisimov et al. report that lifelong administration of rapamycin, starting at 2 mo of age, increases the maximum lifespan of female 129/Sv mice. This finding corroborates, in a different genetic background, the landmark discovery by the National Institute on Aging Intervention Testing Program (ITP) that rapamycin increases mouse lifespan in both sexes when given orally starting at either 9 or 20 mo of age. In contrast to the ITP study, Anisimov et al. administered rapamycin via subcutaneous injection, following a schedule of three injections per week for 2 weeks, followed by a 2 week break. The efficacy of this protocol suggests the intriguing possibility that intermittent administration may be one means of addressing potential side effects of chronic rapamycin usage, an obstacle to the clinical translation of these findings to a practical anti-aging drug in humans. Rapamycin is widely used clinically to suppress immune function during organ transplants, in addition to its use as an anticancer agent. Indeed, the established clinical use of this drug and its analogs represents a crucial opportunity in facilitating the move from basic research on the biology of aging toward agents that could prolong 'healthspan' by protecting against a wide spectrum of age-related diseases, while potentially extending the maximum human lifespan."

STEM CELL ACTIVITY AND MEMORY
Tuesday, February 28, 2012https://www.fightaging.org/archives/2012/02/stem-cell-activity-and-memory.php
Progress in stem cell medicine may lead to ways to restore the capacity for memory lost with aging by intervening in the activity of neural stem cells: researchers "have discovered an answer to the long-standing mystery of how brain cells can both remember new memories while also maintaining older ones. They found that specific neurons in a brain region called the dentate gyrus serve distinct roles in memory formation depending on whether the neural stem cells that produced them were of old versus young age. ... In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging. ... In the study, the authors tested mice in two types of memory processes. Pattern separation is the process by which the brain distinguishes differences between similar events, like remembering two Madeleine cookies with different tastes. In contrast, pattern completion is used to recall detailed content of memories based on limited clues, like recalling who one was with when remembering the taste of the Madeleine cookies. ... Neuroscientists have long thought these two opposing and potentially competing processes occur in different neural circuits. The dentate gyrus, a structure with remarkable plasticity within the nervous system and its role in conditions from depression to epilepsy to traumatic brain injury - was thought to be engaged in pattern separation and the CA3 region in pattern completion. Instead, [researchers] found that dentate gyrus neurons may perform pattern separation or completion depending on the age of their cells."

JUMPSTARTING A COMPROMISED IMMUNE SYSTEM
Monday, February 27, 2012https://www.fightaging.org/archives/2012/02/jumpstarting-a-compromised-immune-system.php
A range of research currently underway focuses on limited but potentially effective ways to reprogram the immune system, so as to work around naturally occurring damage or compromise, or to boost immune system activity when it would do the most good. It's worth keeping an eye on the AIDS research community on this topic, as there are a few broad structural similarities between the aged immune system and the AIDS-compromised immune system: "researchers report on a promising new technique that potentially could turn immune system killer T cells into more effective weapons against infections and possibly cancer. The technique involves delivering DNA into the immune system's instructor cells. The DNA directs these cells to overproduce a specific protein that jumpstarts important killer T cells. These killer cells are typically repressed in patients who have HIV or cancer. ... their technique proved effective in jumpstarting defective immune systems in immuno-compromised mice and in human killer T cells taken from people with HIV. .. In the study, snippets of DNA were delivered into skin instructor cells by a device known as a gene gun. The DNA directed the instructor cells to produce specific proteins, which act like molecular keys. When CD8 T cells interact with the instructor cells, the keys unlock the CD8 T cells' killer properties - jumpstarting them to go out and kill pathogens and cancer cells. With the use of this technique, the killer T cells would not need the assistance of helper T cells. So even if a tumor were to put the helper T cells in a suppressive cage, the killer T cells would still be able to go out and kill cancer cells. Researchers expect that future studies using the technique will make it applicable to many diseases, including cancer."

CALORIE RESTRICTION SLOWS AGING OF THE GASTROINTESTINAL NERVOUS SYSTEM
Monday, February 27, 2012https://www.fightaging.org/archives/2012/02/calorie-restriction-slows-aging-of-the-gastrointestinal-nervous-system.php
Calorie restriction slows more or less every measure of aging, and here is another - a small study to measure decline in the nervous system cells that control a portion of the intestines: "The objective of this study was to evaluate the effects of caloric restriction (CR) on myenteric neurons in the duodenum of Wistar rats during aging. Thirty rats were divided into three groups: the C group (six-month-old animals that were fed a normal diet from weaning until six months of age), the SR group (18-month-old animals that were fed a normal diet from weaning until 18 months of age) and the CR group (18-month-old animals that were fed a 30% CR diet after six months of age). ... The neurons were counted, and the cell body areas were measured. Aging was associated with neuronal loss in the SR group, which was minimized by caloric restriction in the CR group. ... Thus, CR had a protective effect on myenteric neurons during aging."

______________________________

Comments

Post a comment; thoughtful, considered opinions are valued. Please note that comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

All of Fight Aging!, with the exception of the introductory articles, is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite Creative Commons licensed Fight Aging! content in any way you see fit, the only requirements being that you (a) link to the original, (b) attribute the author, and (c) attribute Fight Aging!.